Introduction

Antimicrobials are essential for the treatment of bacterial infections in humans and animals and have revolutionized human healthcare practices worldwide. Penicillin, for instance, lowered mortality linked with pneumococcal pneumonia from 20-40% to 5% and mortality from pneumococcal bacteremia from 50-80% to 18-20% (Laxminarayan et al. 2016). Bacterial resistance to antimicrobials, however, quickly became a substantial clinical problem threatening the advances of the prior decades (Ventola, 2015) and posing a significant threat to public health. When a microorganism that was susceptible to an antibiotic is no longer sensitive due to the acquisition of resistance determinants, antibiotics become less effective and treatment options are limited. This acquired resistance phenotype contrasts with natural resistance presented by several bacteria, which has existed for millions of years, and is an evolutionary consequence of microbial competition in their ecological niches (D’Costa et al., 2011). Bacteria acquire resistance through mutations and horizontal gene transfer of resistance determinants. Direct inactivation of antibiotics (e.g. , by β-lactamases), modification (i.e. , mutation) of cellular targets and modification of cell wall, are examples of resistance strategies/mechanisms that microorganisms employ (Levy and Marshall, 2004). Mutation and mobilization of genes encoding resistance mechanisms, as well as adaptive resistance phenotypes, are fostered by the same factors that promote antibiotic usage, particularly prolonged, cumulative, low-level exposure, including antibiotic overuse, demographic changes associated with urbanization and poor sanitation, discharge of antibiotic residues through environmental wasting and biocide use in livestock production (Marshall and Levy, 2011; Laxminarayan et al., 2013; Woolhouse et al., 2015). Still, antibiotic consumption and overuse are considered the primary drivers of AMR (Klein et al., 2018) and a substantial part of the resistance burden in humans is attributable to antimicrobial use in livestock production, primarily for disease prevention and growth promotion purposes (Marshall and Levy, 2011; Woolhouse et al., 2015). For example, antimicrobials used in livestock are expected to account for circa 80% of the U.S.A. annual antimicrobials consumption (Bartlett et al., 2013) and 73% globally (Van Boeckel et al., 2019).
AMR is now recognized as a complex, multi-layered global problem, that extends beyond national and animal borders, threatening human, animal and environmental health (Queenan et al., 2016; Walsh, 2018; White and Hughes, 2019). Various authors have strongly encouraged a holistic and multidisciplinary “One Health” approach to tackle AMR, while stressing out that the increasing incidence of AMR in humans and livestock has been linked to the emergence of AMR in wildlife (Jones et al., 2008; Wellington et al., 2013). Despite a large, and growing, literature on AMR in the medical and veterinary settings, there is still a dearth of research on the complex transmission dynamics of AMR in the environmental and wild compartments (Allen et al., 2011), even though the range, distribution and number of wild species (only birds (Barrowclough et al., 2016) and mammals (Burgin et al., 2018)) is around 600 times higher than livestock (40 species and 4,500 breeds Barker 1999). Several studies have reported wildlife species as potentially important reservoirs of resistant microorganisms and resistance genes (Arnold et al., 2016; Vittecoq et al., 2016). For example,Escherichia coli  isolates producing extended spectrum beta-lactamases (ESBL) have been isolated from wild boar (Sus scrofa ) in several European countries (Poeta et al., 2009; Krizman et al., 2017; Bonardi et al., 2019), putting at stake the efficacy of beta-lactam antibiotics (e.g. penicillin), which are amongst the most important class of antimicrobial agents used in human and veterinary medicine.
So, there is an urgent missing link, that upon revelation will contribute to the understanding of the origins and roles of antibiotic resistance genes in the gut microbiota of wildlife and the complex transmission dynamics of the underlying determinants in the environmental setting (Allen et al., 2010; Wellington et al.,2013). Howbeit, AMR is deemed as one of the major public health concerns of the 21st century (Woolhouse and Farrar, 2014; Laxminarayan et al., 2016), knowledge concerning AMR bacteria circulating in wildlife is currently limited, although available literature suggests that this wild compartment could provide important insights into AMR emergence and persistence (Allen et al., 2010; Wellington et al., 2013). Theoretically, wild animals are not treated with antibiotics, but their association, both direct and indirect, with humans, livestock, domestic animals or humanized-environments, their ability to easily move across environmental gradients of humanization (from pristine – natural – agroforestry – to highly humanized scenarios), can enhance their contact with selective agents, with commensals from humans and other species, as well as with resistant bacteria. This contact is considered to promote adaptation mechanisms of commensal bacteria and horizontal transfer of resistance genes within the bacterial community of wildlife. Additionally, some of these species (e.g. wild ungulates such as wild boar, among others) are emerging as source of foodborne pathogens in humans due to the manipulation and consumption of game meat (Dias et al., 2015, 2019; Navarro-Gonzalez et al., 2018; Torres et al., 2019b). Altogether, AMR research has to assume a multidisciplinary dimension crossing fields such as microbiology, genomics, environmental science, ecology, agriculture, pharmaceutical industry, synthetic biology, biotechnology and health sciences (Torres et al., 2019a). Neglecting the dialog across different disciplines will hamper our ability to detect, and thus control, the increasing complexities of the factors involved in AMR dynamics.
An analysis that could depict and explore the fact that AMR in wildlife has hitherto received so little attention would be of value, not only to academic researchers but to various stakeholders involved in the topic. The analysis of research trends through bibliometric studies is receiving considerable attention, as they provide valuable information on scientific research and its progression in a specific field of research (Nakagawa et al., 2019). Such analysis allows mapping the structure and accumulation of scientific knowledge in specific fields, allowing the assessment of the evolution of specific disciplines (Zupic and Čater, 2015) by categorizing descriptors such as citations, years, author affiliations, keywords, countries, publication categories, among others (McBurney and Novak, 2002). Previous bibliometric studies on AMR were related to drug-resistance in specific diseases and bacteria (Qin, 2000; Sweileh et al., 2016b, 2016a, 2017b, 2017c, 2017a), disease surveillance programs (Reaves et al., 2017) as well as social impact (Frid-Nielsen et al., 2019).
This study exposes the gaps in the literature relating to the role of wildlife as drivers for the spread of AMR bacteria, by (1) providing a global overview of the spatial and temporal trends of reported scientific knowledge on antimicrobial resistance in wildlife and (2) identifying relevant research gaps both in terms of geographical incidence and also in relation to the subtopics that should be addressed. To deliver such information, peer-reviewed publications of AMR in wildlife were retrieved from the Web of Science, systematized and examined to illustrate the trends and evolutions on this topic.